Moonlighting enzymes: when cellular context defines specificity

Cellular and Molecular Life Sciences, Год журнала: 2023, Номер 80(5)

Опубликована: Апрель 24, 2023

Язык: Английский

---

ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis

Journal of Experimental & Clinical Cancer Research, Год журнала: 2023, Номер 42(1)

Опубликована: Март 22, 2023

Metastases are the major cause of cancer-related morbidity and mortality. By time cancer cells detach from their primary site to eventually spread distant sites, they need acquire ability survive in non-adherent conditions proliferate within a new microenvironment spite stressing that may severely constrain metastatic process. In this study, we gained insight into molecular mechanisms allowing an anchorage-independent manner, regardless both tumor-intrinsic variables nutrient culture conditions.3D spheroids derived lung adenocarcinoma (LUAD) breast were cultured either nutrient-rich or -restricted conditions. A multi-omics approach, including transcriptomics, proteomics, metabolomics, was used explore changes underlying transition 2 3D cultures. Small interfering RNA-mediated loss function assays validate role identified differentially expressed genes proteins H460 HCC827 LUAD as well MCF7 T47D cell lines.We found cultures is associated with significant expression involved metabolic reprogramming. particular, observed tumor spheroid growth implies overexpression ALDOC ENO2 glycolytic enzymes concomitant enhanced consumption glucose fructose production lactate. Transfection siRNA against determined reduction lactate production, viability size produced by H460, HCC827, MCF7, lines.Our results show survival supported drive metabolism towards production. Notably, finding valid for all lines have analyzed different environmental broader Validation mechanism other origin will be necessary broaden types. Future vivo studies assess metastasis.

Язык: Английский

---

Targeting acetyl-CoA carboxylase 1 for cancer therapy

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Фев. 10, 2023

Metabolic adaptation is an emerging hallmark of tumors. De novo fatty acid synthesis important metabolic process to produce intermediates for energy storage, biosynthesis membrane lipids and generation signaling molecules. Acetyl-CoA carboxylase 1 (ACC1) a critical enzyme in the synthesis, which carboxylates acetyl-CoA carboxylic form malonyl-CoA. The role makes it promising therapeutic target various diseases such as non-alcoholic liver disease, obesity diabetes. Tumors have high flow strong dependence on synthesis. Thus, inhibition has become potential choice anti-tumor therapy. In this review, we first introduced structure expression pattern 1. We also discussed molecular mechanisms initiation progression cancer types. Furthermore, carboxylase1 inhibitors been discussed. Collectively, summarized interplay between tumorigenesis, indicating tumor management.

Язык: Английский

---

Cancer immunometabolism: advent, challenges, and perspective

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Апрель 5, 2024

Abstract For decades, great strides have been made in the field of immunometabolism. A plethora evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism center stage innate and adaptive immunomodulation. Given this, we focus changes immunometabolism, a converging series biochemical events that alters immune cell function, propose roles played by diversified metabolic derivatives enzymes, emphasize key metabolism-related checkpoints distinct types, discuss ongoing upcoming realities treatment. It is expected future research will reduce current limitations immunotherapy provide positive hand responses exert broader therapeutic role.

Язык: Английский

---

Glycolysis–Wnt signaling axis tunes developmental timing of embryo segmentation

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 22, 2024

Abstract The question of how metabolism impacts development is seeing a renaissance [1, 2]. How exerts instructive signaling functions one the central issues that need to be resolved. We tackled this in context mouse embryonic axis segmentation. Previous studies have shown changes carbon impact Wnt [3–6] and period segmentation clock [7], which controls timing Here, we reveal glycolysis tunes an anti-correlated manner: higher glycolytic flux slows down clock, vice versa. Transcriptome gene regulatory network analyses identified specifically transcription factor Tcf7l2, previously associated with increased risk for diabetes [8, 9], as potential mechanisms underlying flux-dependent control period. Critically, show deletion antagonist Dkk1 rescued slow phenotype caused by glycolysis, demonstrating instructs In addition, demonstrate metabolic entrainment clock: periodic levels glucose or sentinel metabolite fructose 1,6-bisphosphate (FBP) synchronize oscillations. Notably, FBP pulses first entrained oscillations subsequently Notch hence conclude has immediate, specific effect on signaling. Combined, our work identifies glycolysis-FBP-Wnt developmental timing, highlighting role development.

Язык: Английский

---

Nucleus-translocated GCLM promotes chemoresistance in colorectal cancer through a moonlighting function

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 2, 2025

Язык: Английский

---

Metabolism-driven chromatin dynamics: Molecular principles and technological advances

Molecular Cell, Год журнала: 2025, Номер 85(2), С. 262 - 275

Опубликована: Янв. 1, 2025

Язык: Английский

---

Targeting ceramide transfer protein sensitizes AML to FLT3 inhibitors via a GRP78-ATF6-CHOP axis

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 4, 2025

Язык: Английский

---

Metabolic and Nonmetabolic Functions of PSAT1 Coordinate Signaling Cascades to Confer EGFR Inhibitor Resistance and Drive Progression in Lung Adenocarcinoma

Cancer Research, Год журнала: 2022, Номер 82(19), С. 3516 - 3531

Опубликована: Окт. 4, 2022

Emerging evidence demonstrates that the dysregulated metabolic enzymes can accelerate tumorigenesis and progression via both nonmetabolic functions. Further elucidation of role in EGFR inhibitor resistance metastasis, two leading causes death lung adenocarcinoma, could help improve patient outcomes. Here, we found aberrant upregulation phosphoserine aminotransferase 1 (PSAT1) confers erlotinib tumor metastasis adenocarcinoma. Depletion PSAT1 restored sensitivity to synergistically augmented tumoricidal effect. Mechanistically, inhibition activated ROS-dependent JNK/c-Jun pathway induce cell apoptosis. In addition, interacted with IQGAP1, subsequently activating STAT3-mediated migration independent its activity. Clinical analyses showed expression positively correlated human Collectively, these findings reveal multifunctionality promoting malignancy through activities.Metabolic functions confer promote suggesting therapeutic targeting may attenuate malignant features cancer.

Язык: Английский

---

CD8+ T cell metabolic rewiring defined by scRNA-seq identifies a critical role of ASNS expression dynamics in T cell differentiation

Cell Reports, Год журнала: 2022, Номер 41(7), С. 111639 - 111639

Опубликована: Ноя. 1, 2022

T cells dynamically rewire their metabolism during an immune response. We applied single-cell RNA sequencing to CD8+ activated and differentiated in vitro physiological medium resolve these metabolic dynamics. identify a differential time-dependent reliance of activating on the synthesis versus uptake various non-essential amino acids, which we corroborate with functional assays. also genes that potentially dictate outcome cell differentiation, by ranking them based expression Among them, find asparagine synthetase (Asns), whose peaks for effector decays toward memory formation. Disrupting dynamics ASNS overexpression promotes phenotype, enhancing anti-tumor response adoptively transferred mouse melanoma model. thus provide resource dynamic changes activation as modulator differentiation.

Язык: Английский

---